[Improvement of power and illumination source of the indirect binocular ophthalmoscope designed by Foerster]. / Optimierung von Strom- und Beleuchtungsquelle des indirekten binokularen Brillenophthalmoskops nach Foerster.

BACKGROUND: Since 1982, the indirect binocular ophthalmoscope designed by Foerster has been in use in ophthalmology. The option to implement a new illumination technique using a light-emitting diode (LED) and a new power source should be evaluated in terms of technical feasibility and patient safety. METHODS: The cooling element was redesigned to accommodate the new LED electronics and their components, including an option for a variable brightness control. A more compact rechargeable battery was utilized with variable fixation at the headband or elsewhere. Photometric measurements of light intensity and the operating time were planned. Furthermore, a review of the new lighting technology in terms of EN ISO 15004-2 and EN ISO 10943 was necessary. RESULTS: Technical adjustments to accommodate the LED inside the cooling element could be realised. The power source was a modern rechargeable lithium-ion battery with variable fixation. The luminous intensity of the LED is superior to that of the halogen lamp and the operating time was increased to 520 minutes. The required limits according to DIN EN ISO 15004-2 for ophthalmic devices were met by our measurements. CONCLUSION: The optimisation of the indirect binocular ophthalmoscope brings improvements in illumination intensity and operating time. A conversion for models already in use is possible. A certified appraisal for compliance with the appropriate standards is the next step.

Prognostic relevance of circulating tumor cells in metastatic uveal melanoma.

OBJECTIVE: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. METHODS: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. RESULTS: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. CONCLUSION: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.

[Surgical treatment modalities in uveal melanomas]. / Chirurgische Behandlungsmöglichkeiten beim Aderhautmelanom.

The treatment of large uveal melanomas poses a therapeutic challenge, due to the expected treatment-related side-effects. After sole radiotherapy the majority of patients are faced with radiogenic complications secondary to the large amount of tumour necrosis. Alternative treatment modalities addressing this issue are transscleral resection in arterial hypotension in anteriorly located tumours and endoresection via pars plana vitrectomy in posteriorly located tumours. A surgical resection treatment was applied in 292 patients with large uveal melanomas. In 150 patients the tumour was treated by transscleral resection and postoperative adjuvant (106)ruthenium brachytherapy and 142 patients were treated by primary proton beam irradiation and secondary endoresection. The mean follow-up time was 3.8 and 2.5 years, respectively. Local tumour control was achieved in 76 % and 98 %, respectively. The 5-year metastatic rates were 28 % and 21 % and eye retention was achieved in 82 % and 97 %, respectively. Surgical resection of uveal melanomas with adjuvant radiotherapy is the treatment of choice in cases of large tumours, avoiding enucleation in the vast majority of cases in the long term, without increasing the incidence of tumour-related risks.

[Family screening in patients with retinal angiomatosis]. / Familienuntersuchungen bei Patienten mit Angiomatosis retinae.

BACKGROUND: The aim of this study was to characterise the results of a screening for von Hippel-Lindau disease (VHL), angiomatosis retinae (AR) and further VHL lesions in at-risk relatives of ophthalmological VHL index patients. METHODS: A retrospective analysis of 20 VHL index patients identified by the presence of angiomatosis retinae and a mutation of the VHL gene was carried out. A molecular genetic test for a VHL mutation and funduscopy was offered to all available at-risk relative. In the case of a positive test result, repeated screening for AR and further VHL lesions were suggested. RESULTS: Fifty-one out of 86 first- and second-degree relatives were screened, and 73 % showed a VHL mutation. At first presentation, asymptomatic AR was present in 55 %, at the end of the study in 72 % of gene carriers. In contrast to the index patients, angiomas were small and could be treated without functional loss. During the study 4 eyes of index patients developed blindness, whereas in the affected relatives no such event occurred. Affected relatives developed further VHL lesions to the same number and extent as the index patients. CONCLUSIONS: This study demonstrates the necessity of a screening of at-risk relatives of patients with AR and VHL. Molecular genetic screening allows an early identification of affected relatives. Early and regular screening enables the detection of small retinal angiomas and their treatment without functional loss.

[Primary pars plana vitrectomy. Techniques, indications, and results]. / Primäre Pars-plana-Vitrektomie. Techniken, Indikationen und Ergebnisse.

The choice of primary vitrectomy as the first treatment method for rhegmatogenous retinal detachment has grown in popularity over recent years. The main reason behind this trend is the improved control of more complicated situations of retinal detachment. However, clinical trials comparing primary vitrectomy with scleral buckling had failed to demonstrate an advantage of this method regarding anatomical and functional results. The Scleral Buckling Versus Primary Vitrectomy in Rhegmatogenous Retinal Detachment Study (SPR study) is a prospective, randomised, multicentre study comparing primary vitrectomy with or without additional scleral buckling to scleral buckling alone. Overall, 681 patients with more complicated retinal detachments were recruited in 25 centres. In the phakic subgroup of patients, an advantage regarding the main endpoint (change in visual acuity) was found in the scleral buckling group. In the pseudophakic subgroup, no difference in functional outcome could be seen; however, better anatomical results with a lower rate of retina-affecting reoperations was observed in the vitrectomy group, with particularly good results in the subgroup of patients receiving vitrectomy and additional scleral buckling. Based on the available data, primary vitrectomy combined with a scleral buckle is the method of choice in more complicated types of retinal detachment in pseudophakic patients. In contrast, primary vitrectomy does not seem to offer an advantage over scleral buckling in phakic patients.

[Recurrence rate following adjuvant strontium-90 brachytherapy after excision of conjunctival melanoma]. / Rezidivhäufigkeit nach Exzision von Bindehautmelanomen und adjuvanter Strontium-90-Kontaktbestrahlung.

BACKGROUND: Because of the high local recurrence rates after excision of conjunctival melanomas, adjuvant local chemotherapy or irradiation is recommended. Strontium-90 brachytherapy is one radiotherapeutic option due to its low penetration depth. METHODS: 15 patients with conjunctival melanoma were treated with adjuvant strontium-90 brachytherapy after tumour excision. The treatment was fractionated into 9 irradiation sessions with 6 Gy each. The mean follow-up was 35 months (12-60 months). RESULTS: Seven patients (46%) had no recurrence during the follow-up. Three patients (20%) had a recurrence in the treated or adjacent area. Eight patients (53%) developed new tumours in non-treated areas. CONCLUSIONS: Strontium-90 brachytherapy is a useful adjuvant in the treatment of conjunctival melanomas. Regular ophthalmoscopic controls are necessary because of the high rate of new tumours in non-irradiated areas, especially in cases with primary acquired melanosis.

[Juxtapapillary capillary retinal angioma with epiretinal membrane of the macula in familial Von-Hippel-Lindau-Syndrome]. / Juxtapapilläres kapilläres retinales Angiom mit epiretinaler Membran der Makula bei familiärem Von-Hippel-Lindau-Syndrom.

A case of juxtapapillary capillary retinal angioma associated with a vascularized epiretinal membrane of the macula in a 6-year-old girl is presented. Von-Hippel-Lindau-Syndrome was revealed by molecular genetic methods, and further family members were identified as gene carriers. The retinal angioma embedded in an epiretinal membrane was removed completely with the membrane by pars plana vitrectomy with a good functional result. Histopathology confirmed the diagnosis of capillary angioma.

[Ocular manifestations and surgical results in patients with Marfan syndrome]. / Okuläre Manifestationen und chirurgische Ergebnisse beim Marfan-Syndrom.

AIM: This retrospective study should examine and judge the surgical indications and the therapeutic possibilities as well as their complications in patients with ocular manifestations of Marfan syndrome (MFS) diagnosed according to the criteria of the Ghent nosology. PATIENTS AND METHODS: The study included 17 patients. Operative indications were increasing subluxation of the lens, retinal detachments and secondary glaucoma. The operative procedure depended on patient age and findings. Eleven MFS patients were operated in both eyes and six MFS patients in one eye. RESULTS: Stabilization or functional improvement of visual acuity could be achieved in all patients in whom no disorders limiting visual acuity or amblyopia were present preoperatively. In six eyes of five patients, lens insertion was accomplished via a pars plana approach. Lens removal without implantation of an intraocular lens was performed in 16 eyes of 10 patients. Pars plana vitrectomy was accomplished in 12 eyes. Complications were well controlled by pars plana vitrectomy. CONCLUSIONS: Difficult preoperative situations and postoperative complications are not rare in MFS patients. However, they can be controlled well by means of modern vitreous surgery.

[Photodynamic therapy with verteporfin for uveal melanoma]. / Photodynamische Therapie mit Verteporfin beim Aderhautmelanom Eine klinisch-histopathologische Pilotstudie.

BACKGROUND: The aim of this study was to evaluate whether photodynamic therapy (PDT) with verteporfin is able to induce tumor cell necrosis in human uveal melanomas. METHODS: On four eyes with an uveal melanoma, PDT with verteporfin was performed on the tumor 2-3 days before planned enucleation. The eyes were evaluated histologically. RESULTS: In two melanomas with only mild pigmentation some effects after PDT were detected on tumor tissue in a depth up to 2.5 mm at light doses > or =100 J/cm(2). Histologically, vascular occlusion and thrombosis in tumor vessels were observed. In the heavily pigmented melanoma no tumor necrosis was induced with the above-mentioned parameters. CONCLUSION: Depending on treatment parameters and tumor pigmentation, PDT with verteporfin is able to induce tumor necrosis in human uveal melanomas. Based on these results it is possible that PDT can become an adjuvant treatment method for uveal melanoma.

[Comparison of the anatomical and functional outcome after laser or cryotherapy for retinopathy of prematurity (ROP)]. / Koagulationstherapie bei Frühgeborenenretinopathie Vergleich der anatomischen und funktionellen Ergebnisse nach Laser--oder Kryokoagulation.

PURPOSE: To analyze and compare the anatomical and functional outcome following cryotherapy or laser therapy for ROP. METHODS: Between April 1991 and February 2002, 127 eyes with ROP (65 patients) were treated after threshold ROP was reached. Ten additional eyes with zone I disease were treated with prethreshold. All patients were followed up until a stable retinal situation occurred. RESULTS: An "unfavorable outcome," as described in the Cryo ROP study, occurred in 1 of 91 (1%) eyes with laser treatment and in 3 of 46 (6.5%) eyes with cryotherapy. Temporal dragging of vessels was noticed in 6 of 91 eyes (6.6%) with laser treatment vs 7 of 46 eyes (15.2%) with cryotherapy, respectively. Visual acuity > or =20/25 was achieved in 39.2% in eyes with laser therapy and in 17.6% with cryotherapy (p<0.05). CONCLUSION: A strict screening protocol and treatment at onset of threshold disease results in an excellent anatomical and functional outcome. The results of laser therapy were superior over cryotherapy, indicating that laser treatment is the therapy of choice.

[Photodynamic therapy with verteporfin for recurrent choroidal neovascularisation (CNV) following prior argon laser coagulation]. / Photodynamische Therapie mit Verteporfin bei Rezidiven choroidaler Neovaskularisationen (CNV) nach primärer Argonlaserkoagulation.

BACKGROUND: Photodynamic therapy (PDT) with verteporfin has been successfully introduced to treat choroidal neovascularisations (CNV) that have more than 50% classic CNV components due to exudative age-dependent macular degeneration (AMD) and other diagnoses. However, what is still unclear is if patients with recurrent subfoveal CNV who have had prior laser coagulation can also profit from PDT for CNV. METHODS: The course of visual acuity (ETDRS) and the fluorescein angiographic findings were retrospectively analysed after standard PDT of recurrent subfoveal CNV after prior argon laser coagulation of an extrafoveal or juxtafoveal CNV in AMD or other diagnoses. RESULTS: A total of 20 consecutive eyes from 19 AMD patients were evaluated. After 12 months in 14 of the 20 eyes (70%) deterioration in visual acuity of 3 or more ETDRS lines could be avoided and likewise in 7 of 16 eyes (44%) after 24 months. After the 1st year, 5 of the 7 eyes (71%) with recurrent subfoveal CNV after laser coagulation of a myopic, postinflammatory or idiopathic CNV had deterioration of visual acuity of less than three lines or an improvement in visual acuity. CONCLUSIONS: Despite the low number of patients examined, we could see an indication for PDT in recurrent subfoveal CNV after prior argon laser coagulation of extrafoveal or juxtafoveal CNV. When the patient presented with a CNV cause other than AMD, a better prognosis for visual acuity was achieved.

Selective cone dystrophy with protan genotype.

PURPOSE: To determine the functional defects in two male patients with progressive cone dystrophy and hybrid L-M cone pigment genes. METHODS: Clinical evaluation, standard electroretinography, and electrooculography were performed in two affected patients and two family members. Measurements of spectral sensitivity and transient tritanopia were made in both patients. RESULTS: In the patients, visual acuity varied between 20/50 and 20/100. The electroretinogram showed reduced flicker responses. When light adapted, a-wave amplitudes were borderline, but b-wave amplitudes were reduced severely. Electroretinography with chromatic stimuli showed a difference between well-preserved responses to green and markedly reduced responses to red stimuli. Spectral sensitivity measurement revealed a lack of L (long-wavelength sensitive; red) cone function and normal function of the S (short-wavelength sensitive; blue) and M (middle-wavelength sensitive; green) cones. Transient tritanopia was abnormal, indicating a severe disturbance of cone-cone interaction. CONCLUSIONS: Progressive cone dystrophy with predominant dysfunction of L cones exists in both patients. The cone dystrophy may be caused by a rearrangement of the X-chromosome pigment gene array that is associated with the deletion of L-cone sequences and the formation of hybrid L-M cone pigment genes. It cannot be excluded, however, that both patients have protanopia and that cone dystrophy developed because of other causes.

Radiotherapy of unilateral choroidal metastasis: unilateral irradiation or bilateral irradiation for sterilization of suspected contralateral disease?

Radiotherapy is the highly effective standard in the treatment of choroidal metastasis. Visual acuity can be stabilized or increased in about 70-80% of eyes treated, thus prevailing the quality of life in these worse prognostic patients. In about 30-40% bilateral macroscopic disease is found at diagnosis. The best treatment for unilateral metastasis remains controversial: unilateral or bilateral irradiation for sterilization of suspected contralateral metastasis or unilateral irradiation without irradiation of the contralateral choroidea. In the analysis of a prospective study (ARO 95-08) 35 out of 50 patients with choroidal metastasis had unilateral disease and received unilateral irradiation with a lateral field using 6 MeV-photons (40 Gy in 20 fractions) without sparing the contralateral choroidea. Therefore the posterior contralateral choroidea received 50-70% of the total dose (20-28 Gy) for suspected micrometastasis. None of these patients developed contralateral choroidal metastasis during the median follow up time of 11.5 months. A unilateral field with 40 Gy for unilateral choroidal metastasis without sparing the contralateral choroidea seems to be effective in destroying contralateral micrometastasis with a lower risk of late side effects compared with bilateral fields.

Sympathetic ophthalmia following laser cyclocoagulation.

We describe a 49-year-old white man with sympathetic ophthalmia following contact neodymium-YAG laser cyclotherapy. There was no invasive surgery, and no perforating injuries preceded cyclodestructive therapy. The eye had hemorrhagic secondary glaucoma due to Coats' disease. It was treated three times with contact cyclophotocoagulation after cyclocryotherapy failed to lower intraocular pressure. Subsequently, the intraocular pressure slowly decreased and the eye became phthisical 15 months after the last surgery. Intraocular inflammation developed in the fellow eye and sympathetic ophthalmia was suspected. Histologic and immunohistologic study of the enucleated blind eye confirmed this diagnosis.

Clinicopathologic features of retinoblastoma after primary chemoreduction.

BACKGROUND: Primary chemotherapy is a new treatment approach in retinoblastoma, aiming to avoid radiogenic adverse effects, such as second tumor-associated mortality, as observed following external beam irradiation. OBJECTIVE: To describe the clinical and histopathologic regression pattern after primary chemotherapy in retinoblastoma. METHODS: Five patients with sporadic bilateral retinoblastoma underwent planned enucleation of their functionally blind eye after 2, 3 (in 2 patients), 4, and 6 courses of primary chemotherapy with carboplatin, etoposide, cyclophosphamide, and vincristine. The eyes were examined histopathologically, using light microscopy and immunohistochemical analysis with proliferation markers. RESULTS: One patient had a type 1 (cottage cheese) regression and 4 patients had either a type 2 (fish flesh) or a type 3 (combined) regression pattern. Histopathologic examination revealed a complete tumor necrosis in 1 patient with type 1 regression after 3 courses of chemotherapy and in 1 patient with type 3 regression after 4 courses of chemotherapy. The remaining 3 patients with type 2 or type 3 regression had histologically still active proliferative tumor cells after 2, 3, and 6 courses of chemotherapy. CONCLUSION: This article correlates histopathologically the clinically described efficacy of primary chemotherapy in the treatment of retinoblastoma, underlining, however, the necessity of careful observation and the use of ancillary treatment whenever there is no complete tumor regression.

Transformation of cell type in uveal melanomas: a quantitative histologic analysis.

OBJECTIVE: To describe the cytologic transformation and tumor progression in a series of uveal melanomas. METHODS: Fifteen cases of uveal melanoma, treated by primary transscleral local resection without primary adjuvant treatment, needed enucleation because of local tumor recurrence. Cytologic and cell morphometric features of the primary tumor and the intraocular recurrence were compared, with evaluation of the amounts of intermediate cells, epithelioid cells, mitotic figures, and nucleolar area. RESULTS: The cases were categorized into 2 groups, according to their cytologic characteristics. In the first group (5 cases), there was no cytopathological transformation in the recurrent tumor. The nucleolar area was increased in only 1 case. In the second group (10 cases), the recurrent tumors showed transformation into a more epithelioid cell type. In all but 1 case there was an increase in epithelioid cells in the tumor recurrence. The nucleolar area was increased significantly in all cases. The mean local recurrence interval in all cases was 15.3 months, with no difference between the groups. Death from metastases occurred in 7 cases in which the nucleolar area was 4.2 microm(2) in the primary tumor. CONCLUSIONS: These findings demonstrate that, in an individual tumor, the cytologic phenotype can change considerably even after a relatively short time, resulting in an increase in tumor-related mortality. CLINICAL RELEVANCE: Studies on the natural course of uveal melanoma have been very limited and based purely on observations on the progression of melanomas in terms of size and alteration of various clinical characteristics.

Effect of intravitreal liquid silicone on optic nerve function.

We recorded visual-evoked cortical potentials before and after pars plana vitrectomy and intravitreal liquid silicone filling in 30 patients (30 eyes) with complicated retinal detachments without vascular eye disease or glaucoma. The flash- and flicker-evoked cortical potentials increased in amplitude in all cases. Of 21 eyes followed up for more than 50 days, eight had a 30-Hz flicker response before and after surgery. Of 13 eyes with preoperatively reduced flicker-frequency responses, ten (77%) were improved after surgery. The visual-evoked cortical potential parameters did not deteriorate in any of the patients. We concluded that no toxic effect of intravitreal liquid silicone on the optic nerve could be shown by electrophysiologic methods.

Long-term results of vitrectomy and silicone oil in 500 cases of complicated retinal detachments.

We retrospectively analyzed by life table analysis the visual and functional results in 500 eyes that underwent combined vitrectomy and silicone oil for various types of complicated retinal detachments. The cumulative proportion of eyes with attached retina was 77% at six months postoperatively, with a range of 71% for perforating injuries to 85% for posterior holes. The proportion of eyes with a visual acuity of 5/200 or better was 69% at six months, with a range of 56% for perforating injuries to 81% for posterior holes. Sixty-nine eyes had poor visual function despite an attached retina, primarily because of cataract (18 eyes) and preexisting retinal or optic disease (31 eyes). Visual function in eyes with clear optical media and an attached retina was stable over time, except in patients with diabetes. No clinical evidence of retinal toxicity to silicone oil was noted.

Silicone oil and its influence on electrophysiologic findings.

Twenty patients with complicated retinal detachments who were treated with scleral buckling procedures, vitrectomy, and temporary silicone oil filling underwent electrophysiologic tests before and after silicone oil removal. Electroretinographic responses were markedly low or even absent as long as the silicone oil was in the eye but a few days after silicone oil removal the electroretinographic amplitudes had increased in all 20 patients and did not change significantly thereafter. In 12 patients the basic level of the electrooculogram was low as long as the oil was in the eye but was at least twice the previous value in seven patients after oil removal. A light peak of more than 150% occurred in two patients before oil removal and in six after oil removal.

Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity.

We studied eight patients who had night blindness, maculopathy (often cystoid), degenerative changes in the region of the vascular arcades, relatively mild visual field loss, and an unusual but characteristic electroretinogram. The dark-adapted electroretinogram showed no response to low-intensity stimuli that normally activate the rods, but large, slow responses to high-intensity stimuli. These large, slow waveforms persisted without change under light adaptation, and showed a striking mismatch to photopically balanced short and long wavelength stimuli (with sensitivity much greater to short than long wave-lengths). Since there is evidence from other studies that the electroretinogram and psychophysical responses represent hypersensitivity of short wavelength-sensitive (S or blue) cones, we propose that this disorder be called the enhanced S cone syndrome. There can be different degrees of severity in this syndrome, and progression appears to be slow.